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Effect of Roux-en-Y gastric bypass on the bioavailability of metoprolol from immediate and controlled release tablets: A single oral dose study before and after surgery

Yska, J. P., Wanders, J. T. M., Odigie, B., Apers, J. A., Emous, M., Totté, E. R. E., Boerma, E. C., Ubels, F. L., Woerdenbag, H. J., Frijlink, H. W., Wilffert, B. & Van Roon, E. N., 16-Mar-2019, In : European Journal of Hospital Pharmacy: Science and Practice.

Research output: Contribution to journalArticleAcademicpeer-review

Objective: Roux-en-Y gastric bypass (RYGB) surgery induces major changes in the gastrointestinal tract that may alter the pharmacokinetics of orally administered drugs. Results from pharmacokinetic studies are sparse. This study aimed to investigate the effect of RYGB on the bioavailability of metoprolol from immediate release (IR) and controlled release (CR) tablets in female patient volunteers before and after surgery. Methods: An explorative, two-phase, single oral dose pharmacokinetic study of metoprolol in female patients undergoing RYGB was carried out. The dose was administered twice in each patient, 1 month before and 6 months after surgery. After intake of either 100 mg of metoprolol IR or CR tablet serum concentration-time profiles of metoprolol were determined. The endpoint was the ratio of AUCafter/AUCbefore of metoprolol. Results: Twelve patients were included in the study (metoprolol IR: 7; metoprolol CR: 5). After intake of a metoprolol IR tablet major intraindividual and interindividual differences for area under the serum concentration versus time curve (AUC) of metoprolol before and after surgery were observed (range ratio AUC0-10 hours after/AUC0-10 hours before: 0.74-1.98). For metoprolol CR tablets a significant reduction in bioavailability of metoprolol was observed after surgery (range ratio AUC0-24 hours after/AUC0-24 hours before: 0.43-0.77). Conclusion: RYGB may influence the bioavailability of metoprolol from an IR tablet. The magnitude of changes in bioavailability after RYGB requires close monitoring of patients using metoprolol IR tablets and dose adjustment if deemed necessary. RYGB clearly reduces the bioavailability of metoprolol from a CR tablet. After RYGB clinicians may consider to increase the dose according to clinical response.
Original languageEnglish
JournalEuropean Journal of Hospital Pharmacy: Science and Practice
Publication statusPublished - 16-Mar-2019

    Keywords

  • bioavailability, controlled release, gastric bypass surgery, immediate release, metoprolol, pharmacokinetics, adult, article, AUC (0-24 h), clinical article, clinician, controlled study, drug therapy, female, human, human tissue, monitoring, oral drug administration, plasma concentration-time curve, Roux-en-Y gastric bypass, tablet, volunteer

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